Virtually all prior attempts to study the psychobiology of recovery in depression longitudinal may have been confounded by the direct and/or remote effects of somatic forms of therapy. During the past 35 months we have unmedicated patients during the recovery process. To date, 75 patients (5(0 outpatients and 16 inpatients) with primary endogenous unipolar major depression have been studies. Although nearly 80% of patients responded, there was only limited evidence of normalization of EEG sleep abnormalities. Post-treatment studies revealed that 60% of treatment responders manifested two or more common EEG sleep abnormalities (poor sleep efficiency, diminished slow wave sleep, reduced REM latency, or increased REM density), suggesting that some abnormalities may persist as traits or scars of depressive vulnerability. Contrary to our initial hypothesis, we found that several EEG sleep features of endogenous depression were correlated with more rapid or complete improvement. Our findings thus support the continued use of CBT in service of psychobiological research. These observations raise new questions: Will a more severely disturbed sample show greater evidence of state-dependent change in EEG sleep and hypothalamic-pituitary-adrenal axis (HPA) disturbances? and Will residual EEG sleep abnormalities eventually normalize with sustained recovery? In order to address these questions, an intensive form of CBT was developed for use with more severely depressed hospitalized patients and a 2-year follow-up of remitted outpatients is underway. During the proposed 2-year competing renewal, two interrelated protocols will be studies: Study 1 will evaluate the psychobiology of recovery in 24 unmedicated hospitalized major depressives (assessed pre-and post- treatment with EEG sleep and HPA studies) treated with an intensive 28- day CBT protocol; Study 2 is a 2-year prospective follow-up of 70 CBT responders (50 outpatient; 20 inpatient), with repeat EEG sleep studies after 1 and 2 years of sustained recovery and at times of relapse. We hypothesize that acute response will lead to a disaggregation of state- dependent psychobiologic abnormalities (e.g., indices of hypercortisolism, increases RED density, and poor sleep efficiency) from variables which may represent traits or scars (e.g., reduced REM latency or diminished delta sleep). Further, the persistence of apparently trait-like (state-independent) abnormalities even after 2 years of sustained recovery is predicted. Results of these studies will have significance in clarifying the nature of psychobiologic disturbances across the course of depressive episode (e.e., from illness to remission to recovery and will provide new data concerning predictors of relapse and correlates of nonresponse to nonsomatic therapy.